The chemical mechanism of non-enzymatic RNA polymerization

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In the earliest stages of the development of life, before the evolution of complex RNA or protein enzymes, the genetic information stored in nucleic acids had to be copied without the help of sophisticated catalysts. A common model for this process is the template-directed polymerization of imidazole-activated nucleotides from the 3’-end of a primer. Despite decades of studies on this system, the precise chemical mechanism of polymerization has not been determined. In particular, magnesium is a critical component of the reaction, but we do not understand the interplay between its potential roles in activating the 3’-hydroxyl, orienting the reaction center and helping monomers bind. I will present recent results from experiments that address these questions. I will also discuss what these results tell us about the optimal conditions for the non-enzymatic replication of RNA.